Purpose of reviewFTY720, a synthetic myriocin analogue derived from culture filtrates ofIsaria sinclairii, is a novel immunosuppressant that in experimental animals, nonhuman primates, and renal transplant recipients produces lymphocytopenia and prolongs allograft survival in a dose-dependent fashion. Furthermore, the synergistic interactions of FTY720 promote the immunosuppressive effects of calcineurin antagonists and/or proliferation signal inhibitors, providing the possibility of reducing exposure to and thereby ameliorating the toxicity of these drugs.Recent findingsThe likely mechanism of action of FTY720 is induction of lymphocytopenia owing to migration from peripheral blood to secondary lymphoid structures. This mechanism involves binding to sphingosine-1-phosphate receptors on lymphocytes followed by involvement of the sphingosine transporter Abcb1 (Mdr1), the leukotriene C4transporter Abcc1, 5-lipoxygenase, and Rho. In humans, FTY720 reduces the incidence of acute rejection episodes and apparently produces only one significant toxicity: bradycardia. Phase III studies of FTY720 are ongoing to explore the potential advantages suggested by the results of earlier trials: high oral bioavailability, low interindividual variations in exposures at a constant dose, and the absence of collateral toxicities associated with other immunosuppressants (disturbed lipid metabolism, diabetes mellitus, nephrotoxicity, neurotoxicity, and myelosuppression).SummaryFTY720 is an archetype of a new class of agents that alter lymphocyte adhesion and migration and disrupt the participation of chemokines in inflammatory processes. FTY720 is likely to play an important future role by synergizing with other agents, yielding less toxic immunosuppressive regimens.